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Article: Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies
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TitlePotent neutralization of Hendra and Nipah viruses by human monoclonal antibodies
 
AuthorsZhu, Z2 4
Dimitrov, AS3
Bossart, KN1 3
Crameri, G1
Bishop, KA3
Choudhry, V4
Mungall, BA1
Feng, YR3
Choudhary, A3
Zhang, MY2 4
Feng, Y4
Wang, LF1
Xiao, X4
Eaton, BT1
Broder, CC3
Dimitrov, DS4
 
Issue Date2006
 
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
 
CitationJournal Of Virology, 2006, v. 80 n. 2, p. 891-899 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.80.2.891-899.2006
 
AbstractHendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 μg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 μg/ml, and 98% neutralization required only 1.6 μg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
 
ISSN0022-538X
2013 Impact Factor: 4.648
 
DOIhttp://dx.doi.org/10.1128/JVI.80.2.891-899.2006
 
ISI Accession Number IDWOS:000234382900035
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhu, Z
 
dc.contributor.authorDimitrov, AS
 
dc.contributor.authorBossart, KN
 
dc.contributor.authorCrameri, G
 
dc.contributor.authorBishop, KA
 
dc.contributor.authorChoudhry, V
 
dc.contributor.authorMungall, BA
 
dc.contributor.authorFeng, YR
 
dc.contributor.authorChoudhary, A
 
dc.contributor.authorZhang, MY
 
dc.contributor.authorFeng, Y
 
dc.contributor.authorWang, LF
 
dc.contributor.authorXiao, X
 
dc.contributor.authorEaton, BT
 
dc.contributor.authorBroder, CC
 
dc.contributor.authorDimitrov, DS
 
dc.date.accessioned2012-08-08T08:49:54Z
 
dc.date.available2012-08-08T08:49:54Z
 
dc.date.issued2006
 
dc.description.abstractHendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 μg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 μg/ml, and 98% neutralization required only 1.6 μg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Virology, 2006, v. 80 n. 2, p. 891-899 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.80.2.891-899.2006
 
dc.identifier.doihttp://dx.doi.org/10.1128/JVI.80.2.891-899.2006
 
dc.identifier.epage899
 
dc.identifier.isiWOS:000234382900035
 
dc.identifier.issn0022-538X
2013 Impact Factor: 4.648
 
dc.identifier.issue2
 
dc.identifier.pmid16378991
 
dc.identifier.scopuseid_2-s2.0-30344474011
 
dc.identifier.spage891
 
dc.identifier.urihttp://hdl.handle.net/10722/157431
 
dc.identifier.volume80
 
dc.languageeng
 
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Virology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAntibodies, Monoclonal - Biosynthesis - Immunology
 
dc.subject.meshAntibodies, Viral - Biosynthesis - Immunology
 
dc.subject.meshAntibody Specificity
 
dc.subject.meshCross Reactions
 
dc.subject.meshDose-Response Relationship, Immunologic
 
dc.subject.meshEpitopes - Immunology
 
dc.subject.meshGlycoproteins - Immunology
 
dc.subject.meshHendra Virus - Chemistry - Immunology
 
dc.subject.meshHumans
 
dc.subject.meshImmunoglobulin Fab Fragments - Immunology
 
dc.subject.meshImmunoglobulin G - Immunology
 
dc.subject.meshNeutralization Tests
 
dc.subject.meshNipah Virus - Immunology
 
dc.subject.meshPeptide Library
 
dc.subject.meshSolubility
 
dc.subject.meshViral Envelope Proteins - Immunology
 
dc.titlePotent neutralization of Hendra and Nipah viruses by human monoclonal antibodies
 
dc.typeArticle
 
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Author Affiliations
  1. CSIRO Livestock Industries
  2. SAIC-Frederick
  3. Uniformed Services University of the Health Sciences
  4. National Institutes of Health, Bethesda